The basic helix-loop-helix (HLH) transcription factor called activated B cell factor 1 (ABF-1) is expressed in a subset of lymphoid tissues, including lymph nodes, activated B cells and Epstein-Barr virus-transformed B cell lines designated as lymphoblastoid cell lines (LCLs). The viral protein Epstein-Barr virus 2 (EBNA-2) has been identified as a potential regulator of the ABF-1 gene. The proposed studies are aimed at investigating the role of EBNA-2 and its influence on ABF-1 gene activity, and the identification of ABF-l-regulated target genes in B cells. A broad spectrum of genetic and biochemical techniques will be used, including gene cloning and sequencing, DNA microarray analysis, DNA transfections, electrophoretic-mobility shift assays, Western- and Northern blotting and quantitative real-time polymerase chain reaction (PCR). The results of these studies will enhance our understanding of the mechanisms by which EBNA-2 controls cellular gene expression and B-cell immortilization.